What is the RIC?

The Cardiovascular Research Network is an association that comprises more than 800 researchers from all over Spain. Organized in 64 research groups, they develop their scientific and educational activities based on seven research programs. The main goal of the association is to reduce the impact that cardiovascular diseases have over the survival and life quality of Spanish citizens, promoting research and the implementation of the results obtained into the daily clinical practice. The current Network “RIC” is the result of the association of three research networks (RECAVA, REDINSCOR y HERACLES) that are part of the Instituto de Salud Carlos III. All of them have a networked research experience of more than 10 years.

PROGRAMS

Programme 1: Research programme on adverse ventricular remodeling.

Coordinador: Francisco Fernández-Avilés Díaz.

Adverse ventricular remodeling (AVR) is used to describe a variety of changes in the biophysiology of the cardiomyocyte, the volume and composition of cardiomyocyte and noncardiomyocyte compartments, and the geometry and architecture of the ventricular chambers that occur in response to myocardial infarction, pressure or volume overload, cardiomyopathic states, exposure to infectious or cardiotoxic agents, etc. AVR is a key determinant of the clinical course of a number of cardiac diseases finally evolving with heart failure (HF). AVR and HF is a major public health problem in Spain and throughout the world. This has led us to propose this programme to further understand the biology and basic mechanisms underlying AVR, explore humoral and imaging biomarkers of the disease, identify potential novel targets, apply the information and concepts available in clinical studies of patients and, develop other biotechnological novel applications to prevent or reverse AVR that leads to HF. Objectives of this programme are:

Explore new molecular and cellular mechanisms in AVR.

Developing and testing new biochemical and imaging biomarkers in order to improve identification, diagnosis, therapy response and outcomes of patients with AVR.

Developing new therapeutic targets. 4) Developing clinical trials in order to prevent or reverse AVR.

Ischemic heart disease is the leading cause of death in Spain; its total cost in Spain is estimated in 326.000 €/year(Ministry of Health, 2006). The main single pathophysiological mechanism through which coronary artery disease causes mortality and morbidity is the death of cardiac cells occurring during episodes of myocardial ischemia due to intracoronary thrombosis secondary to plaque erosion, fissuring or rupturing. Thus, limiting cardiomycyte death has a priority objective to limit the social impact of this disease. This objective can be differently approached: preventing reperfusion injury; preventing or limiting plaque complications; and limiting the magnitude and persistence of coronary thrombosis secondary to plaque complication. Objectives during this programme are:

To improve our knowledge of the mechanisms of reperfusion injury, and the genetic and ambiental factors modulating it, and to develop treatments effective and safe in patients with myocardial infarction.

To improve our understanding of the molecular mechanisms of plaque progression, complication and intracoronary thrombosis to allow de development of new therapeutic strategies.

To develop, through epidemiological approaches, methods to identify patients at risk of developing ischemic heart disease, plaque complication, and adverse evolution, and to assess the outcomes of managements of patients with acute coronary syndrome.

Programme 3: Research program on aortic aneurysm: from molecular mechanisms to new diagnostic and therapeutic approaches.

Coordinador: Arturo Evangelista.

Progressive aortic dilatation is not very symptomatic but is associated with a very high morbidity and mortality. The aetiology can be genetic or congenital or acquired. Both conditions share a common pathway leading to the deterioration of the integrity of the aortic wall and formation of aneurysm. Aneurysm, defined as permanent dilatation of the aorta is due to abnormal vascular remodeling resulting in loss of structural integrity leading to progressive, permanent and focal dilatation and ultimately risk of rupture. Study of the aortic disease, integrating genetic, clinical and imaging data, biomarkers and understanding of the pathophysiologic mechanisms inherent in the different aetiologies may significantly further understanding the aortic dilatation progression, predictors of complications and the most appropriate pharmacological or surgical therapeutic strategy. Objectives of this programme are:

To investigate the role of genetic, haemodynamic and risk factors in the development of aorticaneurysms.

To identify the molecular and biological mechanisms leading to progressive aortic dilatation.

To develop new therapeutic strategies guided by genetic and biomechanical markers in the management of aortic aneurysms.

Inherited cardiovascular diseases (ICVD) are a group of heart diseases that includes cardiomyopathies and channelopathies. They are characterized by their genetic component and familial presentation; in these diseases the clinician has not to think on a single individual, but in a family. Furthermore, their clinical presentation is highly variable but the first clinical manifestation could be sudden death. Some of these ICVD are considered rare diseases, and there is a lack of knowledge in its diagnosis, prognosis and treatment. Nevertheless, it is estimated that in Spain more than 150,000 people suffer from an ICVD and one of each four spanish citizens that suffers from an ICVD is not aware of that. Objectives of this programme are:

To improve diagnosis, clinical management, treatment and risk stratification in ICVD that would prevent cardiac sudden death and improve quality of life of these patients.

To facilitate the creation of a large cohort of patients with ICVD that will give rise to complete family studies with the adequate methodology and capacity to respond to the questions raised by researchers.

To integrate the activities of different clinical and basic research groups, in these rare diseases, to obtain more efficient and higher clinical and scientific impact.

Programme 5 - Research programme on identification and characterization of the processes that lead to the development of the arrhythmic substrate in the scar tissue programme.

Coordinador: Ángel Arenal Maíz

The mechanism underlying sustained Ventricular tachycardias (VT) in patients with chronic myocardial infarction ornonischemic dilated myocardiopathy is a reentry in which the slow conduction pathways are composed of bundles of viable myocytes embedded in myocardial scars. Sudden cardiac death due to VT is a major cause of mortality in these patients with structural heart disease. Therefore, studies focused on the structure and cellular characteristics of the myocardial scar could enable us to prevent the development of VT substrate and to stratify the risk of arrhythmia. Objectives of this programme are:

To organize a platform to study the development and differential characteristics of the scar and heterogeneous tissue in patients with structural heart disease and VT.

To develop experimental models of post infarction VT to study the characteristics of the scar associated with the VT substrate and their progression over time.

To identify the mechanism that determines the appearance of VT substrate and changes over time of the scar.

To develop image techniques to characterize the scar to identify the VT substrate and stratify the arrhythmic risk.

To identify biomarkers to monitor the extension and progression of scar and heterogeneous tissue.

To design experimental models of regional scar related VT to test and develop therapies to prevent the appearance and stop the progression of VT substrate.

To design human studies to develop therapies to prevent the appearance and stop the progression of VT substrate.

Heart failure (HF) is one of the most prevalent, fatal, and resource demanding cardiac disorders. According to the 2010 Report of the Spanish Ministry of Health, in Spain HF is the 4th leading cause of hospitalization and consumes about 3% of the healthcare budget. The mortality rate at 4 years is about 50%,comparable to more aggressive cancer types. Current gaps in clinical management of HF requiring further research are, among others, the imprecise knowledge of the mechanism and treatment of HF with preserved systolic left ventricular function, the undefined treatment of cardiorenal syndrome, the not yet settled clinical role of biomarker-guided treatment of HF, the need for out-hospital management models for fragile and severe HF patients, the delayed recognition of cardiac graft rejection, and uncertainties in patient selection for complex and costly therapies. Moreover, the genetic, metabolic, and cellular electro-mechanical derangements in the different types of HF need to be better delineated. Objectives of this programme are:

To improve knowledge, prognosis, and care cost-benefit of heart failure and heart transplantation.

To organize a multicenter scientific and technologic horizontal platform able to conduct clinical and translational research on heart failure and heart transplantation.

To gain insight into the pathophysiology and management of heart failure, pulmonary arterial hypertension, and cardiac allograft rejection using combined clinical, genetic, and biological approaches.

To identify the most appropriate patient candidates for complex and costly therapies in order to improve the prognosis and care cost-benefit of heart failure and heart transplantation.

To investigate new ways of pro-inflammatory cardiac cell activation and cellular derangements of the nuclear-cytoplasmatic kinetics and calcium handling in the human failing heart.

Programme 7 - Research programme on prevention of cardiovascular diseases and study of hypertension mechanisms.

Coordinador: Jaume Marrugat de la Iglesia

Coronary artery disease (CAD) is the single most common cause of death in Europe, accounting for 2.18 million deaths yearly (27% of all deaths in persons >69 years). Annual CAD costs exceed €49 billion in the EU. These figures indicate how much could be saved in resources and years of life if CAD incidence and mortality could be reduced. Hypertension is one of the most common chronic diseases in clinical practice, affecting more than 1 billion people worldwide. Its complications (stroke, heart failure, kidney disease) are major sources of morbidity and mortality. A substantial proportion of patients treated for hypertension do not achieve the blood pressure control. Thus, developing a more precise understanding of the molecular pathogenesis of hypertension is a pressing priority for translational research. Objectives of this programme are:

To study the mechanisms of hypertension in the development of atherosclerosis and related cardiovascular diseases.

Improvement of cardiovascular risk functions for primary prevention.

Development of predictive functions of prognosis for acute coronary syndrome, stroke and congestive heart failure.

To study metabolic pathways of blood pressure impact on atherosclerosis and related diseases.

INSTITUCIONAL VIDEO

This is how we are. The biggest structure of cooperative cardiovascular research in our country, formed by the higher number of scientists researching in a network, seeking solutions to cardiovascular problems of the current society and developing training plans to create reliable translational researches.